Circulating immune complexes, insulin antibodies, and deposits of immunoglobulins in the skin in diabetes.

Sixty-five insulin-dependent diabetes mellitus (IDDM) patients at the Steno-Memorial Hospital entered the present study. Of these, 43.1 percent had one or more late diabetic complication, 19.3 percent had circulating immune complexes (CIC)--there was a tendency for CIC to be related to late diabetic complications (P = 0.1) - and 16.9 percent had elevated total S-IgG. Elevated S-IgG values were related neither to CIC, to complications, nor to IgG deposits in the skin. Three patients had elevated total S-IgM, IgD and, IgE, respectively. No patients had elevated total S-IgA. Insulin antibodies were present in 41.9 percent. They were related to neither CIC nor clinical complications. No patients had rheumatoid factors (RF) or granulocyte-specific antinuclear antibodies (ANA). 12.3 percent had a low titre of organ non-specific ANA. No relationship could be established between ANA and complications or CIC. As regards skin deposits IgG was present at the dermo-epidermal junction zone (DEJ) and/or in the dermal vessels in 75.4 percent of the patients; IgA was present in 35.4 percent; and IgM in 32.3 percent. IgD and IgE were absent in all patients. Fibrinogen deposits were found in 80 percent and complement C3 in 32.3 percent. No correlation was found between skin deposits and CIC, on one hand, or clinical complications, on the other. From the present work, we conclude that humorally mediated immunological processes are active in IDDM. However, the exact role of this activity still remains to be defined.

Basophil histamine release by nuclear components in chronic bronchitis and bronchial asthma of intrinsic type.

The involvement of an allergic reaction directed against nuclear components and aggregated IgG was examined by basophil histamine release technique in chronic bronchitis (CB) in the intrinsic type of bronchial asthma (IA). In the group of 21 CB patients, seven responded to RNA, DNA or histone and three responded to aggregated IgG. In the other group of seven IA patients one responded to RNA and histone. In comparison with healthy blood donors the prevalence of smooth muscle antibodies was increased in CB patients and antinuclear antibodies were increased in both groups of patients. The findings suggest an involvement of an allergic reaction directed against RNA, DNA, histone, and aggregated IgG in some patients with CB and IA. This may play some role in the reversible airway obstruction of these diseases.

Basophil histamine release by RNA, DNA and aggregated IgG examined in rheumatoid arthritis and systemic lupus erythematosus. Results compared with basophil counts and antinuclear antibodies.

Basophils from patients with rheumatoid arthritis (RA) respond to RNA, DNA and immune complexes (aggregated IgG) with histamine release. The RNA response was well correlated to the clinical activity of the disease, since histamine liberation was found in all patients with severe activity, whereas no liberation was observed in patients with moderate or quiescent activity. A less significant correlation was obtained with DNA and aggregated IgG. In contrast, no response was obtained with RNA, DNA and aggregated IgG in patients with systemic lupus erythematosus (SLE) or in controls. In the RA and the SLE groups no significant correlation was found between the response of RNA, DNA and aggregated IgG and the serum titres of anti-DNA and antinuclear antibodies. No difference in basophil cell count in peripheral blood and basophil histamine content was found between RA, SLE and controls. Our results point to an involvement of an autoimmune type I reaction in the pathogenesis of RA directed against the nuclear components RNA and DNA and against immune complexes.

Immunofluorescence of the skin in allergic diseases: an investigation of patients with contact dermatitis, allergic vasculitis and atopic dermatitis.

Skin biopsies for immunofluorescent studies were taken from patients with contact dermatitis (positive patch tests), atopic dermatitis and allergic vasculitis for comparison with normal-appearing skin from the same patients, and from healthy controls. A variety of deposits of immunoglobulins, complement components and fibrinogen were demonstrated in 6 out of 20 patients with contact dermatitis, 7 out of 10 with atopic dermatitis, 8 out of 10 with allergic vasculitis, and in 4 out of 20 control individuals. No diagnostic pattern of deposits was found. Elevated serum IgE and eosinophilic counts were found in patients with atopic dermatitis, and high serum IgA and fibrinogen levels were found in the allergic vasculitis group.

Immune complexes in cystic fibrosis.

Eleven patients with cystic fibrosis (CF) chronically infected with mucoid P. aeruginosa and ten patients without P. aeruginosa infection were examined for occurrence of circulating immune complexes, for immune complex deposits in the dermo-epidermal junction of the skin and for precipitins against P. aeruginosa, S. aureus, H. influenzae and D. pneumoniae antigens. The serum concentrations of haptoglobin, orosomucoid, immunoglobulins, C1q, C3, C4 and total haemolytic complement, antinuclear and rheumatoid factor activities as well as white blood cell counts and erythrocyte sedimentation rates were determined also. The results indicated that 6 patients from the chronically P. aeruginosa infected group, exhibiting a spectrum of serum precipitins against P. aeruginosa antigens, also had immune complexes in the serum, while only one patient (suffering from selective IgA deficiency) in the group without P. aeruginosa infection was positive for soluble immune complexes. Granular deposits of IgM was found in the skin of 10 of the chronically P. aeruginosa infected patients and in 7 of the patients without P. aeruginosa infection. A few pactients in both groups had dermo-epidermal deposits of C1q, C3 or fibrinogen as well. Eight of the patients in the chronically infected group and five in the group without P. aeruginosa infection had organ non-specific antinuclear factors. The haptoglobin levels appeared to be elevated in the chronically infected patients (p less than 0.05). None of the other parameters showed any significant difference between the two groups.

Immune deposits in the dermo-epidermal junction in rheumatoid arthritis.

Skin biopsies from forty patients with rheumatoid arthritis were studied for presence of immune deposits in the dermo-epidermal junction zone. In about half of these unselected patients with classical and definite rheumatoid arthritis, IgM, complement components and fibrinogen antigenic material were found. A positive correlation is demonstrated between immune deposits and the presence of cryoglobulins in serum. The presence of complement components in the skin deposits was found to be clearly related to the clinical activity of the disease, as judged by Lansbury's index.

Lymphocyte chimerism after bone marrow transplantation. Surface markers and in vitro function of donor and recipient lymphocyte subpopulations.

Specific HLA antibodies were used to eliminate donor and recipient cells, respectively, from lymphocyte suspensions prepared from the blood of a child who had been transplanted with bone marrow from an HLA-A- and HLA-B-incompatible, HLA-D-compatible donor. About 70% of the lymphocytes were of donor HLA type, the remaining of recipient type. The phytohemagglutinin-responsive lymphocytes were exclusively limited to the lymphocyte population carrying donor-type HLA antigens. Membrane immunofluorescence investigations of the donor and recipient populations showed a low percentage of IgM-positive lymphocytes in the donor population and an extremely high proportion of IgM-positive lymphocytes in the recipient population. About 90% of the donor lymphocytes were T cells, as judged by their capacity to form rosettes between sheep erythrocytes and T lymphocytes; no cells in the recipient cell population expressed this ability.

Immunoglobulin deposits in the dermo-epidermal junction zone in patients with systemic lupus erythematosus. Rheumatoid arthritis and temporal arteritis compared by serological testing including alpha2-macroglobulin.

In biopsies from normal-looking skin, immune complexes in the dermo-epidermal junction zone were found by a direct immunofluorescence technique in 14 of 17 patients with systemic lupus erythematosus, in 6 of 12 patients with rheumatoid arthritis, but in none of 10 patients with temporal arteritis and 25 normal controls. Blood samples were obtained simultaneously from all patients and high titres of IgG organ-nonspecific antinuclear factors with complement-fixing properties were found to be closely related to systemic lupus erythematosus. IgG granulocyte-specific antinuclear factors were related with rheumatoid arthritis, while high concentrations of plasma fibrinogen were characteristic of temporal arteritis. No significant increases or differences in blood values of alpha2-macroglobulin were found between the groups and no correlation was found with deposits in the skin.

Thymectomy as immunosuppression in uremic patients.

Five uremic patients awaiting renal transplantation underwent transcervical thymectomy in an evaluation of the immunosuppressive effect of removal of the thymus in such transplantations. A number of immunological parameters, including lymphocyte transformation tests, were followed in these patients for up to 30 weeks after thymectomy. The number of B lymphocytes in the blood, stem cells in bone marrow, and T lymphocytes in lymph nodes decreased, whereas IgG, IgA, and IgM in four cases and C3 complement in all five cases increased. Blood leucocyte and lymphocyte counts did not show any characteristic changes. The T cell response of circulating lymphocytes was determined after stimulation with mitogens, specific antigens, and allogeneic cells in mixed lymphocyte culture, and showed a large increase. Thymectomy of uremic patients results in a considerable increase in immunocompetence in the first 30 weeks, indicating that it is not suitable as an immunosuppressive treatment.